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Distinct Resting-State Functional Connectivity Profiles in ADHD with and without Prenatal Alcohol Exposure

Gupta, I.; Farkouh, L.; Kilpatrick, L. A.; Korthas, J.; Salamon, N.; Schneider, B. N.; Joshi, S. H.; Alger, J. R.; O'Connor, M. J.; O'Neill, J.

2026-05-26 psychiatry and clinical psychology
10.64898/2026.05.25.26354061 medRxiv
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Aim: To determine whether the neural phenotype (whole-brain resting-state functional connectivity pattern) of attention deficit hyperactivity disorder associated with prenatal alcohol exposure (ADHD+PAE) differs from that in unexposed children with ADHD of probable familial origin (ADHD-PAE). Method: Resting-state functional MRI was acquired from 26 children with ADHD+PAE, 25 with ADHD-PAE, and 25 typically developing (TD) children, all aged 8-13 years. Mean connectivity matrices based on the Cole-Anticevic Brainwide Network Parcellation of the brain were compared between the groups. Results: Within the frontoparietal network (FPN), children with ADHD+PAE showed widespread lower group-mean connectivity than children with ADHD-PAE; effects were concentrated primarily in cerebellar-cerebral cortical and cerebral cortical-cerebral cortical connections. Children with ADHD-PAE showed widespread hyperconnectivity relative to TD children. Children with ADHD+PAE showed mixed hyper- and hypoconnectivity relative to TD. Interpretation: These results are consistent with other MRI findings indicating that ADHD+PAE is neurally distinct from ADHD-PAE; PAE may be associated with broadly reduced connectivity, especially across cerebellar-cerebral cortical systems.

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